Imidazo[1,2-a] pyridine derivatives and their application as pharmaceuticals

ABSTRACT

Imidazo[1,2-a] pyridines of the formula: ##STR1## and their acid addition salts in which Y represents a hydrogen or halogen atom or a C 1-4  alkyl radical, Z represents a naphthyl radical or a radical ##STR2## in which each of X 1  and X 2  independently of one another is a hydrogen or halogen atom, a C 1-4  alkoxy radical, a C 1-6  alkyl radical or CF 3 , CH 3  S--, CH 3  SO 2  --, --NO 2 , --NH 2  or --NHCOCH 3 , and each of R 1  and R 2  independently of one another represents a hydrogen atom, a straight or branched C 1-5  alkyl radical which is unsubstituted or substituted by one or more halogen atoms or hydroxyl, --N(C 1-4  alkyl) 2 , carbamoyl or C 1-4  alkoxy radicals, allyl, propargyl, a C 3-6  cycloalkyl radical, benzyl, or phenyl, not both R 1  and R 2  being hydrogen, or --NR 1  R 2  represents a heterocyclic ring containing from 3 to 6 carbon atoms, or a heterocyclic ring of the formula ##STR3## in which X is O, S, CHOR&#39; or &gt;N--R, R&#39; being hydrogen or benzyl and R being hydrogen, a C 1-4  alkyl radical, or phenyl which is unsubstituted or substituted by methoxy or a halogen atom, which may be made from the corresponding acids, have valuable pharmacological properties, especially anxiolytic, anti-anoxic, sleep-inducing, hypnotic and anticonvulsant properties.

DESCRIPTION

The present invention relates to imidazo [1,2-a] pyridine derivatives,useful in therapy and their preparation.

Imidazo [1,2-a] pyridines have already been described in the literature,for example in British Pat. Nos. 991,589 and 1,076,089 and in variousother publications.

The compounds of the present invention have the formula (I) ##STR4##

in which Y represents a hydrogen or halogen atom or a C₁₋₄ alkylradical, Z represents a naphthyl radical or a radical ##STR5## in whicheach of X₁ and X₂ independently of one another is a hydrogen or halogenatom, a C₁₋₄ alkoxy radical, a C₁₋₆ alkyl radical or CF₃, CH₃ S, CH₃ SO₂or NO₂ and each of R₁ and R₂ independently of one another represents ahydrogen atom, a straight or branched C₁₋₅ alkyl radical which isunsubstituted or substituted by one or more halogen atoms, hydroxyl,N(C₁₋₄ alkyl)₂, carbamoyl or C₁₋₄ alkoxy radicals, an allyl radical, apropargyl radical, a C₃₋₆ cycloalkyl radical, a benzyl radical or aphenyl radical, not both R₁ and R₂ being hydrogen, or NR₁ R₂ representsa heterocyclic ring containing from 3 to 6 carbon atoms, or aheterocyclic ring of the formula, ##STR6## in which X is O, S, CHOR'or >NR, R' being hydrogen or benzyl and R being hydrogen, a C₁₋₄ alkylradical or phenyl which is unsubstituted or substituted by methoxy or ahalogen atom.

The preferred compounds of the invention are those in which R₁ and R₂are both alkyl radicals. Amongst these compounds, those in which Y is inthe 6-position and represents either a halogen atom or the methylradical are particularly preferred. Finally, amongst the lattercompounds, there may be mentioned those in which Z is a radical ##STR7##in which X₁ is a halogen atom or the radical CH₃.

According to a feature of the invention, the compounds of formula (I)can be prepared according to the following reaction scheme: ##STR8##

The reaction for the conversion of the nitrile (II) to the primary amideis carried out in accordance with a conventional method, for examplewith the aid of an acid such as dry hrdrogen chloride, in a solvent suchas formic acid, at a temperature from 15° to 50° C.

The saponification of the primary amide (III) to the acid (IV) may becarried out in ethanolic potassium hydroxide at the reflux temperature.

The conversion of the acid (IV) to the amide compound of formula (I) iscarried out in accordance with any suitable method, for example byreacting the acid (IV) with the amine HNR₁ R₂, in the presence ofcarbonyldiimidazole, or by reacting the chloride of the acid (IV) withthe amine HNR₁ R₂.

The general method for the preparation of the starting nitriles (II) isdescribed in the literature, in particular in British Pat. No.1,076,089.

The following Examples illustrate the present invention. The analysesand the IR and NMR spectra confirm the structure of the compounds.

EXAMPLE 1

6-Chloro-2-(4-chlorophenyl)-imidazo[1,2-a]-pyridine-3-N,N-dimethylacetamide. ##STR9##

1. 22 g (0.0788 mol) of6-chloro-2-(4-chlorophenyl)-imidazo[1,2-a]pyridine-3-acetonitrile areadded to 85 ml of 99% formic acid and the solution is treated with astream of dry hydrogen chloride for 3 to 4 hours. When all the nitrilehas been converted, the solution is heated slightly to degas it, and thecooled solution is then poured into 1 liter of water; the mixture isstirred for 10 minutes and then rendered alkaline with 200 ml ofconcentrated ammonia solution. The solid is filtered off, washedcopiously with water and dried under a waterpump vacuum. The6-chloro-2-(4-chlorophenyl)-imidazo[1,2-a]pyridine-3-acetamide isrecrystallised from ethanol. Melting point=285°-7° C.

2. 19.2 g of6-chloro-2-(4-chlorophenyl)-imidazo[1,2-a]pyridine-3-acetamide and 19 gof KOH are added successively to 550 ml of 75% ethanol. The suspensionis heated at the reflux temperature for 10-16 hours. When the reactionhas ended, the solution is concentrated in vacuo and the residue isdissolved in 1/2 liter of water. The small amount of insoluble materialis filtered off and the filtrate is treated with 50 ml of acetic acid.The expected acid precipitates and it is filtered of and roughly dried.The crude product is taken up in 500 ml of acetone and the6-chloro-2-(4-chlorophenyl)-imidazo[1,2-a]pyridine-3-acetic acid isfiltered off hot. Melting point=258°-260° C.

3. 4 g (12.45 millimols) of6-chloro-2-(4-chlorophenyl)-imidazo[1,2-a]pyridine-3-acetic acid and2.42 g (14.94 millimols) of carbonyldiimidazole are suspended in 60 mlof dry tetrahydrofuran. The reaction mixture is stirred at 20° C. untilthe evolution of carbon dioxide has ended, and is then heated gently at40° C. for 15 minutes and cooled to 0° C. A solution of 14.94 millimolsof dimethylamine in 5 ml of tetrahydrofuran is then added. Thesuspension is stirred for 15 minutes at 20° C. and then concentrated;the residue is treated with 300 ml of water and 50 ml of a saturatedaqueous solution of NaHCO₃. The insoluble material is filtered off,washed with water and dried. The compound obtained is recrystallisedfrom a solvent such as ethanol. Melting point=230° C.

EXAMPLE 2 4-Methyl-1{[2-(4-chlorophenyl)-imidazo[1,2-a]pyridin-3-yl]methylcarbonyl}-piperazine. ##STR10##

4.5 g (15.64 millimols) of2-(4-chlorophenyl)-imidazo[1,2-a]pyridine-3-acetic acid are added to asuspension of N,N-dimethyl-chloro-methyleneiminium chloride prepared byadding 2.2 g (17.75 millimols) of oxalyl chloride to 30 ml ofdimethylformamide (DMF) at -10° C. The suspension is stirred for 15minutes at 0° C. and a solution of 5.4 g (54 millimols) of4-methylpiperazine in 10 ml of dry DMF is then added gradually theretoat 0° C. The solution is stirred for 8 hours and then poured into 750 mlof water. The amide is extracted with CH₂ Cl₂, the organic phase isdried over Na₂ SO₄ and concentrated, the residue is passed through asilica column (eluant: CH₂ Cl₂ /CH₃ OH 9/1) and the compound obtained isrecrystallised from an isopropyl ether/acetonitrile mixture. Meltingpoint=175° C.

The compounds listed in the following Table were similarly prepared.

                                      TABLE                                       __________________________________________________________________________     ##STR11##                                                                                                     Melting                                                                       point                                        Compound                                                                            Y   Z         NR.sub.1 R.sub.2                                                                           (°C.)                                 __________________________________________________________________________    1     H   4-ClC.sub.6 H.sub.4                                                                     NHCH.sub.3   234                                          2     H   4-ClC.sub.6 H.sub.4                                                                     N(CH.sub.3).sub.2                                                                          179                                          3     H   4-ClC.sub.6 H.sub.4                                                                      ##STR12##   187-8                                        4     H   4-ClC.sub.6 H.sub.4                                                                      ##STR13##   190                                          5     H   4-ClC.sub.6 H.sub.4                                                                      ##STR14##   175                                          6     H   3-CF.sub.3C.sub.6 H.sub.4                                                                ##STR15##   157.5-158                                    7     H   4-ClC.sub.6 H.sub.4                                                                      ##STR16##   206-7                                        8     H   4-ClC.sub.6 H.sub.4                                                                      ##STR17##   242                                          9     6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     NHCH.sub.3   >290                                         10    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     NHC.sub.2 H.sub.5                                                                          280-2                                        11    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     NHn-C.sub.3 H.sub.7                                                                        229-30                                       12    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     NHi-C.sub.3 H.sub.7                                                                        259                                          13    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     NHn-C.sub.4 H.sub.9                                                                        225                                          14    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     NHt-C.sub.4 H.sub.9                                                                        224                                          15    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                      ##STR18##   243-5                                        16    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     NHC.sub.6 H.sub.5                                                                          265-7                                        17    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     NHCH.sub.2 C.sub.6 H.sub.5                                                                 253-4                                        18    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     NHCH.sub. 2 CH.sub.2 OH                                                                    260-1                                        19    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     NHCH.sub.2 CH.sub.2 OCH.sub.3                                                              197                                          20    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     NHCH.sub.2 CH.sub.2 N(CH.sub.3).sub.2                                                      199-201                                      21    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     NHCH.sub.2 CHCH.sub.2                                                                      233                                          22    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     NHCH.sub.2CCH                                                                              239                                          23    6-Cl                                                                              4-CH.sub.3C.sub.6 H.sub.4                                                               NHC.sub.2 H.sub.5                                                                          238                                          24    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     NHCH.sub.2 CF.sub.3                                                                        258                                          25    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     NHCH.sub.2 CONH.sub.2                                                                      256-7                                        26    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     N(CH.sub.3).sub.2                                                                          230                                          27    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     N(C.sub.2 H.sub.5).sub.2                                                                   149                                          28    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     N(n-C.sub.3 H.sub.7).sub.2                                                                 140-1                                        29    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                      ##STR19##   160                                          30    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                      ##STR20##   185-6                                        31    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     N(n-C.sub.4 H.sub.9).sub.2                                                                 149-150                                      32    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                      ##STR21##   243-5                                        33    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                      ##STR22##   219-220                                      34    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                      ##STR23##   208-9                                        35    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                      ##STR24##   190-2                                        36    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                      ##STR25##   >300                                         37    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                      ##STR26##   204-6                                        38    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                      ##STR27##   262                                          39    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                      ##STR28##   239-241                                      40    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                      ##STR29##   270                                          41    6-CH.sub.3                                                                        4-ClC.sub.6 H.sub.4                                                                     NHCH.sub.3   261-2                                        42    6-CH.sub.3                                                                        4-ClC.sub.6 H.sub.4                                                                     NHC.sub.2 H.sub.5                                                                          224-5                                        43    6-CH.sub.3                                                                        4-ClC.sub.6 H.sub.4                                                                     NHCH.sub.2 CH.sub.2 OH                                                                     246                                          44    6-CH.sub.3                                                                        4-ClC.sub.6 H.sub.4                                                                     N(CH.sub.3).sub.2                                                                          215                                          45    6-CH.sub.3                                                                        4-ClC.sub.6 H.sub.4                                                                     NHCH.sub.2CH.sub.2Cl                                                                       202                                          46    6-CH.sub.3                                                                        4-ClC.sub.6 H.sub.4                                                                      ##STR30##   194                                          47    6-Cl                                                                              C.sub.6 H.sub.5                                                                         NHCH.sub.3   276-7                                        48    6-Cl                                                                              C.sub.6 H.sub.5                                                                         N(CH.sub.3).sub.2                                                                          192                                          49    6-Cl                                                                              4-CH.sub.3C.sub.6 H.sub.4                                                               NHCH.sub.3   277-8                                        50    6-Cl                                                                              4-CH.sub.3C.sub.6 H.sub.4                                                               N(CH.sub.3).sub.2                                                                          185-6                                        51    6-Cl                                                                              4-CH.sub.3 OC.sub.6 H.sub.4                                                             NHCH.sub.3   273                                          52    6-Cl                                                                              4-CH.sub.3 OC.sub.6 H.sub.4                                                             N(CH.sub.3).sub.2                                                                          166                                          53    6-Cl                                                                              4-BrC.sub.6 H.sub.4                                                                     NHC.sub.2 H.sub.5                                                                          287                                          54    6-Cl                                                                              4-BrC.sub.6 H.sub.4                                                                     N(C.sub.2 H.sub.5).sub.2                                                                   168                                          55    6-Cl                                                                              naphth-2-yl                                                                              ##STR31##   217-8                                        56    6-Cl                                                                              naphth-2-yl                                                                              ##STR32##   193-4                                        57    6-Cl                                                                              naphth-1-yl                                                                             N(CH.sub.3).sub.2                                                                          187-8                                        58    6-Cl                                                                              2-CH.sub.3C.sub.6 H.sub.4                                                               NHCH.sub.3   175-6                                        59    6-Cl                                                                              2-CH.sub.3C.sub.6 H.sub.4                                                               NHC.sub.2 H.sub.5                                                                          161-2                                        60    6-Cl                                                                              2-CH.sub.3 OC.sub.6 H.sub.4                                                             NHC.sub.2 H.sub.5                                                                          172-3                                        61    6-Cl                                                                              3-ClC.sub.6 H.sub.4                                                                     NHC.sub.2 H.sub.5                                                                          215-6                                        62    6-Cl                                                                              3-CH.sub.3 OC.sub.6 H.sub.4                                                             N(C.sub.2 H.sub.5).sub.2                                                                   98-9                                         63    6-Cl                                                                              3-CH.sub.3 OC.sub.6 H.sub.4                                                              ##STR33##   190                                          64    6-Cl                                                                              3,4-Cl.sub.2C.sub.6 H.sub.3                                                             N(CH.sub.3).sub.2                                                                          221-2                                        65    6-Cl                                                                              3,4-(CH.sub.3 O).sub.2C.sub.6 H.sub.3                                                   N(CH.sub.3).sub.2                                                                          215                                          66    6-Cl                                                                              3,4-(CH.sub.3 O).sub.2C.sub.6 H.sub.3                                                   N(n-C.sub.3 H.sub.7).sub.2                                                                 147                                          67    7-CH.sub.3                                                                        4-ClC.sub.6 H.sub.4                                                                     NHC.sub.2 H.sub.5                                                                          228                                          68    7-CH.sub.3                                                                        4-ClC.sub.6 H.sub.4                                                                     N(CH.sub.3).sub.2                                                                          206                                          69    8-CH.sub.3                                                                        4-ClC.sub.6 H.sub.4                                                                     NHCH.sub.3   234                                          70    8-CH.sub.3                                                                        4-ClC.sub.6 H.sub.4                                                                     N(C.sub.2 H.sub.5).sub.2                                                                   175,5                                        71    6-Cl                                                                              4-FC.sub.6 H.sub.4                                                                      N(CH.sub.3).sub.2                                                                          210                                          72    6-Cl                                                                              4-FC.sub.6 H.sub.4                                                                      N(n-C.sub.4 H.sub.9).sub.2                                                                 129                                          73    6-CH.sub.3                                                                        4-FC.sub.6 H.sub.4                                                                      N(CH.sub.3).sub.2                                                                          195                                          74    6-Cl                                                                              4-BrC.sub.6 H.sub.4                                                                     N(CH.sub.3).sub.2                                                                          228-9                                        75    6-CH.sub.3                                                                        4-CH.sub.3C.sub.6 H.sub.4                                                               N(CH.sub.3).sub.2                                                                          196                                          76    6-CH.sub.3                                                                        4-ClC.sub.6 H.sub.4                                                                     N(n-C.sub.4 H.sub.9).sub.2                                                                 116                                          77    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                      ##STR34##   152                                          78    H   4-ClC.sub.6 H.sub.4                                                                     N(n-C.sub.3 H.sub.7).sub.2                                                                 136                                          79    H   4-ClC.sub.6 H.sub.4                                                                     N(n-C.sub.4 H.sub.9).sub.2                                                                 105                                          80    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                     N(n-C.sub.5 H.sub.11).sub.2                                                                92-3                                         81    6-CH.sub.3                                                                        4-CH.sub.3C.sub.6 H.sub.4                                                               NHCH.sub.3   187                                          82    6-CH.sub.3                                                                        4-CH.sub.3C.sub.6 H.sub.4                                                               NHC.sub.2 H.sub.5                                                                          184                                          83    6-CH.sub.3                                                                        4-CH.sub.3 C.sub.6 H.sub.4                                                               ##STR35##   108                                          84    6-CH.sub.3                                                                        4-CH.sub.3 C.sub.6 H.sub.4                                                              N(n-C.sub.3 H.sub.7).sub.2                                                                 115                                          85    6-CH.sub.3                                                                        4-CH.sub.3C.sub.6 H.sub.4                                                                ##STR36##   168                                          86    6-CH.sub.3                                                                        4-ClC.sub.6 H.sub.4                                                                     NHCH.sub.2 CF.sub.3                                                                        239                                          87    6-CH.sub.3                                                                        4-BrC.sub.6 H.sub.4                                                                     NHC.sub.2 H.sub.5                                                                          232-4                                        88    6-CH.sub.3                                                                        4-BrC.sub.6 H.sub.4                                                                     N(CH.sub.3).sub.2                                                                          203.5-205                                    89    6-CH.sub.3                                                                        4-BrC.sub.6 H.sub.4                                                                     N(n-C.sub.3 H.sub.7).sub.2                                                                 138-9                                        90    6-CH.sub.3                                                                        4-BrC.sub.6 H.sub.4                                                                      ##STR37##   195.5-197                                    91    6-CH.sub.3                                                                        4-CH.sub.3 O C.sub.6 H.sub.4                                                            N(CH.sub.3).sub.2.CH.sub.3 SO.sub.3 H                                                      230-2                                        92    6-CH.sub.3                                                                        4-CH.sub.3 SC.sub.6 H.sub.4                                                             N(CH.sub.3).sub.2.CH.sub.3 SO.sub.3 H                                                      209                                          93    6-CH.sub.3                                                                        4-CH.sub.3 SO.sub.2C.sub.6 H.sub.4                                                      N(CH.sub.3).sub.2                                                                          227-9                                        94    6-CH.sub.3                                                                        4-NO.sub.2C.sub.6 H.sub.4                                                               NHC.sub.2 H.sub.5                                                                          268-270                                      95    6-CH.sub.3                                                                        4-NO.sub.2C.sub.6 H.sub.4                                                               N(CH.sub.3).sub.2                                                                          262-3                                        96    6-CH.sub.3                                                                        4-t-C.sub.4 H.sub.9C.sub.6 H.sub.4                                                      N(CH.sub.3).sub.2                                                                          199-200                                      97    6-Cl                                                                              4-ClC.sub.6 H.sub.4                                                                      ##STR38##   173                                          __________________________________________________________________________

The compounds of the invention were subjected to pharmacologicalexperiments which showed their valuable pharmacological properties invarious areas.

The toxicity of the compounds was determined on mice by intraperitonealadministration. The LD 50 ranges from 500 to 1,000 mg/kg.

The anxiolytic activity was determined according to the eating test (R.J. Stephens, (1973), Brit. J. Pharmac., 49, 146 P). In this test, thedoses which increases the food consumption of the mice vary from 0.1 to10 mg/kg, administered intraperitoneally.

The activity of the compounds in the area of cerebral circulation wasdetermined in the test for the hypoxia caused by pressure reduction.Mice of the CD1 strain are kept in an oxygen-depleted atmosphereproduced by creating a partial vacuum (190 mm of mercury, correspondingto 5.25% of oxygen). The survival time of the animals is noted. Thistime is increased by agents which are capable of assisting theoxygenation of tissues and in particular of the brain. The compoundsstudied are administered intraperitoneally in several doses, 10 minutesbefore the experiment. The percentage increases in the survival time,relative to the values obtained for control animals, are calculated. Themean active dose (MAD), that is to say the dose which increases thesurvival time by 100%, is determined graphically. The MAD ranges from0.3 to 32 mg/kg, administered intraperitoneally.

The anticonvulsant activity was determined in accordance with the testfor the antagonism towards the mortality induced by bicuculline in mice(P. Worms, H. Depoortere and K. G. Lloyd, (1979) Life Sci., 25,607-614). The products to be studied are injected intraperitoneally, 30minutes before the bicuculline (0.9 mg/kg, administered intravenously).With death being the criterion selected for this test, the percentagemortalities are noted for each batch, 2 hours after administration ofthe bicuculline (control batch: 100% mortality). For each product, the50% active dose (AD 50 or the dose which protects 50% of the animalsfrom the lethal effects of the bicuculline) is determined graphically.The AD 50 of the compounds of the invention vary between 0.3 and 30mg/kg, administered intraperitoneally.

The sedative or hypnotic activity was determined by observing the actionof the compounds on the EEG of curarised rats and also on the wake-sleepstates in freely moving, implanted rats and cats (H. Depoortere, Rev.E.E.G. Neurophysiol., (1980) 10, 3, 207-214; L. M. Da Costa, H.Depoortere and R. Naquet, Rev. E.E.G. Neurophysiol., (1977), 7, 2,158-164). In curarised rats, the products to be studied were injectedintraperitoneally or orally at doses increasing from 0.1 to 30 mg/kg.They induce sleep traces starting from doses ranging from 0.1 to 10mg/kg, administered intraperitoneally or orally. In freely moving,implanted rats, the products to be studied were injectedintraperitoneally or orally at a single dose ranging from 1 to 10 mg/kg.At these doses, they reduce the total wake time by 13 to 44%, withoutsignificantly changing the total paradoxical sleep time, certainproducts even increasing the total duration of this phase of sleep. Infreely moving, implanted cats, the products to be studied were injectedintraperitoneally or orally at a single dose of 10 mg/kg. Theytransitorily increase the wake time after injection, this beingaccompanied by benzodiazepine-type jactation, and reduce the totalparadoxical sleep time by 40 to 100%. However, certain products increasethe total duration of the SWSP (slow-wave sleep with phase phenomena:P.G.O. points) by about 50%.

The results of these various tests show that the compounds of theinvention possess anxiolytic, anti-anoxic, sleep-inducing, hypnotic andanticonvulsant propertis; the compounds of the invention are useful forthe treatment o anxiety states, sleep disorders and other neurologicaland psychiatric complaints, for the treatment of vigilance disorders, inparticular for combating behavioural disorders which can be attributedto cerebral vascular damage and to the cerebral sclerosis encountered ingeriatrics, and also for the treatment of epileptic vertigo due tocranial traumatisms and for the treatment of metabolic encephalopathies.

The compounds of the invention can be presented in any form which issuitable for oral or parenteral administration, for example in the formof tablets, coated tablets, capsules, solutions to be taken orally orinjected, and the like, with any suitable excipient. The daily posologycan range from 0.5 to 2,000 mg.

What is claimed is:
 1. A compound of the formula ##STR39## wherein X₁ ishalogen or methyl;Y is hydrogen, halogen or methyl; R₁ is hydrogen, C₁₋₅alkyl or hydroxy (C₁₋₅ alkyl); and R₂ is C₁₋₅ alkyl or hydroxy (C₁₋₅alkyl)or a pharmaceutically acceptable salt thereof.
 2. Animidazo[1,2-a]pyridine according to claim 1, in which R₁ and R₂ are bothalkyl radicals.
 3. An imidazo[1,2-a]pyridine according to claim 2, inwhich Y is chlorine or methyl.
 4. A method of providing a patient with ahypnotic effect which comprises administerinng to said patient ahypnotically-effective amount of a compound of the formula: ##STR40##wherein X₁ is halogen or methyl;Y is hydrogen, halogen or methyl; R₁ ishydrogen, C₁₋₅ alkyl or hydroxy (C₁₋₅ alkyl); and R₂ is C₁₋₅ alkyl orhydroxy (C₁₋₅ alkyl)or a pharmaceutically acceptable salt thereof.
 5. Amethod of claim 4 wherein R₁ and R₂ are alkyl.
 6. A method of claim 5wherein Y is chlorine or methyl.
 7. A method of providing a patient withan anxiolytic effect which comprises administering to said patient ananxioloytically-effective amount of a compound of the formula: ##STR41##wherein X₁ is halogen or methyl;Y is hydrogen, halogen or methyl; R₁ ishydrogen, C₁₋₅ alkyl or hydroxy (C₁₋₅ alkyl); and R₂ is C₁₋₅ alkyl orhydroxy (C₁₋₅ alkyl) or a pharmaceutically acceptable salt thereof.
 8. Amethod of claim 7 wherein R₁ and R₂ are alkyl.
 9. A method of claim 8wherein Y is chlorine or methyl.
 10. A method of providing a patientwith an anticonvulsive effect which comprises administering to saidpatient an anticonvulsive dosage of a compound of the formula: ##STR42##wherein X₁ is halogen or methyl;Y is hydrogen, halogen or methyl; R₁ ishydrogen, C₁₋₅ alkyl or hydroxy (C₁₋₅ alkyl); and R₂ is C₁₋₅ alkyl orhydroxy (C₁₋₅ alkyl) or a pharmaceutically acceptable salt thereof. 11.A method of claim 10 wherein R₁ and R₂ are alkyl.
 12. A method of claim11 wherein Y is chlorine or methyl.